Pancreatitis is a disease of which the onset is triggered by activation of pancreatic enzymes in pancreas, so that pancreas is auto-digested by activated pancreatic enzymes. As therapeutic agents of pancreatitis, use is made of for example gastric acid secretion suppressing agents, proteinase inhibiting agents, analgesics and anti-spasmodics, antibiotics and the like (Practice of Gastro-Intestinal Diagnostics 6, edited by Tadahiko Kozu, chief editor, Bunkodo, Tokyo, 1993).
More specifically, histamine H.sub.2 receptor antagonists (blockers) including cimetidine, ranitidine, famotidine and the like are used as gastric acid secretion suppressing agents (Therapeutic Medicine Guide, '96 edition, edited by Medical Practice Editorial Committee, Bunkodo, Tokyo, 1996). Proteinase inhibiting agents include high-molecular urinastatin extracted from human urine and gabexate mesilate and nafamostat mesilate as lower molecular synthetic products Mebio, 13(6), 74-80 (1996)!. As the analgesics and anti-spasmodics, use is made of non-steroidal, anti-inflammatory analgesics (indomethacin) and non-opioid analgesics (pentazocine). As the antibiotics, use is made of penicillin-series antibiotics with wide spectrum (piperacillin), and cefem-series antibiotics of first and second generations (cefazolin and cefmetazole) (Practice of Gastro-Intestinal Diagnostics 6, edited by Tadahiko Kozu, chief editor, Bunkodo, 1993). However, the pharmacological effects of any of these pharmaceutical agents are not sufficient. Thus, more excellent prophylactic or therapeutic agents of pancreatitis have been needed.
Adenosine causes various physiological effect through receptor (A.sub.1, A.sub.2A, A.sub.2B, A.sub.3) which present on plasma membrane. Adenosine uptake inhibitor maintains adenosine concentration around adenosine receptor and increase adenosine effect by inhibiting adenosine uptake into tissue.
Most of quinazoline derivatives represented by the following formula (I) to be used in accordance with the present invention have been known, and it has been known also that such derivatives have an adenosine uptake inhibitory activity and are effective for myocardial protection and prophylaxis or treatment of inflammation such as paw edema (WO94/19342, WO96/06841). Additionally, Chemical Pharmaceutical Bulletin, 38, 1591-1595 (1990) describes a 1,2,3,4-tetrahydro-2,4-dioxoquinazoline derivative with 1-(6,7-dimethoxy-4-quinazolyl)-4-piperidinyl group at position 3 and hydrogen, chloride atom or nitro group at position 6.
It has also been known that an N-aryl piperazine alkaneamide derivative with some relation to the compound represented by the following Formula (II) has various pharmacological actions. More specifically, Japanese Published Examined Patent Application No.232/69 describes that the derivative has coronary vasodilator action, central stimulant action, local anesthetic action, or anti-carrageenan action; Japanese Published Unexamined Patent Application No. 4774/83 describes that the derivative has an action of myocardial protection; Japanese Published Unexamined Patent Application No. 290869/88 describes that the derivative has an action of ameliorating sleep quality; and European Journal of Pharmacology, 172, 273-281 (1989) describes that the derivative has an action of inhibiting adenosine uptake. Furthermore, Japanese Published Unexamined Patent Application No. 157472/94 describes that N-piperazine acetamide derivatives of 4,5-diphenyloxazol, thiazole and imidazole have an action of inhibiting adenosine uptake and a neuroprotective action. Still additionally, Nucleosides & Nucleotides, 10, 975-982 (1991) describes that dipyridamole, dilazep, hexobendine, lidoflazine and R75231 have an action of inhibiting adenosine uptake.
However, it has not yet been known that the compound represented by Formula (I) or Formula (II) is effective for the prophylaxis or treatment of pancreatitis. No report has been published yet, indicating that a compound with an action of inhibiting adenosine uptake is effective for the prophylaxis or treatment of pancreatitis.